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Razavi P, Baldwin G, Garg I, Velazquez LM, Garcia M, Gan J, Choi H, Zeng R, Vingopoulos F, Husain D, Kim LA, Patel NA, Miller JB. Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2024;Abstract
PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.
Schwartzman JA, Lebreton F, Salamzade R, Shea T, Martin MJ, Schaufler K, Urhan A, Abeel T, Camargo ILBC, Sgardioli BF, Prichula J, Frazzon APG, Giribet G, Van Tyne D, Treinish G, Innis CJ, Wagenaar JA, Whipple RM, Manson AL, Earl AM, Gilmore MS. Global diversity of enterococci and description of 18 previously unknown species. Proc Natl Acad Sci U S A 2024;121(10):e2310852121.Abstract
Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.
Martinez Sanchez M, Chan W-M, MacKinnon SE, Barry B, Hunter DG, Engle EC, Whitman MC. Presence of Copy Number Variants Associated With Esotropia in Patients With Exotropia. JAMA Ophthalmol 2024;Abstract
IMPORTANCE: Strabismus is a common ocular disorder of childhood. There is a clear genetic component to strabismus, but it is not known if esotropia and exotropia share genetic risk factors. OBJECTIVE: To determine whether genetic duplications associated with esotropia are also associated with exotropia. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted from November 2005 to December 2023. Individuals with constant or intermittent exotropia of any magnitude or a history of surgery for exotropia were recruited from pediatric ophthalmic practices. Data were analyzed from March to December 2023. EXPOSURE: Genetic duplication. MAIN OUTCOMES AND MEASURES: Presence of genetic duplications at 2p11.2, 4p15.2, and 10q11.22 assessed by digital droplet polymerase chain reaction. Orthoptic measurements and history of strabismus surgery were performed. RESULTS: A total of 234 individuals (mean [SD] age, 19.5 [19.0] years; 127 female [54.3%]) were included in this study. The chromosome 2 duplication was present in 1.7% of patients with exotropia (4 of 234; P = .40), a similar proportion to the 1.4% of patients with esotropia (23 of 1614) in whom it was previously reported and higher than the 0.1% of controls (4 of 3922) previously reported (difference, 1.6%; 95% CI, 0%-3.3%; P < .001). The chromosome 4 duplication was present in 3.0% of patients with exotropia (7 of 234; P = .10), a similar proportion to the 1.7% of patients with esotropia (27 of 1614) and higher than the 0.2% of controls (6 of 3922) in whom it was previously reported (difference, 2.8%; 95% CI, 0.6%-5.0%; P < .001). The chromosome 10 duplication was present in 6.0% of patients with exotropia (14 of 234; P = .08), a similar proportion to the 4% of patients with esotropia (64 of 1614) and higher than the 0.4% of controls (18 of 3922) in whom it was previously reported (difference, 5.6%; 95% CI, 2.5%-8.6%; P < .001). Individuals with a duplication had higher mean (SD) magnitude of deviation (31 [13] vs 22 [14] prism diopters [PD]; difference, 9 PD; 95% CI, 1-16 PD; P = .03), were more likely to have constant (vs intermittent) exotropia (70% vs 29%; difference, 41%; 95% CI, 20.8%-61.2%; P < .001), and had a higher rate of exotropia surgery than those without a duplication (58% vs 34%; difference, 24%; 95% CI, 3%-44%; P = .02). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, results suggest that the genetic duplications on chromosomes 2, 4, and 10 were risk factors for exotropia as well as esotropia. These findings support the possibility that esotropia and exotropia have shared genetic risk factors. Whether esotropia or exotropia develops in the presence of these duplications may be influenced by other shared or independent genetic variants or by environmental factors.
Whalen M, Akula M, McNamee SM, Deangelis MM, Haider NB. Seeing the Future: A Review of Ocular Therapy. Bioengineering (Basel) 2024;11(2)Abstract
Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range. While gene, cell, and antibody therapy and nanoparticle delivery directly treat regions that have been damaged by disease, they can be limited in the duration of the therapeutic delivery and have a focal effect. In contrast, contact lenses and ocular implants can more effectively achieve sustained and widespread delivery of therapies; however, they can increase dilution of therapeutics, which may result in reduced effectiveness. Current therapies either offer a sustained release or a broad therapeutic effect, and future directions should aim toward achieving both. This review discusses current ocular therapy delivery systems and their applications, mechanisms for delivering therapeutic products to ocular tissues, advantages and challenges associated with each delivery system, current approved therapies, and clinical trials. Future directions for the improvement in existing ocular therapies include combination therapies, such as combined cell and gene therapies, as well as AI-driven devices, such as cortical implants that directly transmit visual information to the cortex.
Huang AS, Hirabayashi K, Barna L, Parikh D, Pasquale LR. Assessment of a Large Language Model's Responses to Questions and Cases About Glaucoma and Retina Management. JAMA Ophthalmol 2024;Abstract
IMPORTANCE: Large language models (LLMs) are revolutionizing medical diagnosis and treatment, offering unprecedented accuracy and ease surpassing conventional search engines. Their integration into medical assistance programs will become pivotal for ophthalmologists as an adjunct for practicing evidence-based medicine. Therefore, the diagnostic and treatment accuracy of LLM-generated responses compared with fellowship-trained ophthalmologists can help assess their accuracy and validate their potential utility in ophthalmic subspecialties. OBJECTIVE: To compare the diagnostic accuracy and comprehensiveness of responses from an LLM chatbot with those of fellowship-trained glaucoma and retina specialists on ophthalmological questions and real patient case management. DESIGN, SETTING, AND PARTICIPANTS: This comparative cross-sectional study recruited 15 participants aged 31 to 67 years, including 12 attending physicians and 3 senior trainees, from eye clinics affiliated with the Department of Ophthalmology at Icahn School of Medicine at Mount Sinai, New York, New York. Glaucoma and retina questions (10 of each type) were randomly selected from the American Academy of Ophthalmology's Commonly Asked Questions. Deidentified glaucoma and retinal cases (10 of each type) were randomly selected from ophthalmology patients seen at Icahn School of Medicine at Mount Sinai-affiliated clinics. The LLM used was GPT-4 (version dated May 12, 2023). Data were collected from June to August 2023. MAIN OUTCOMES AND MEASURES: Responses were assessed via a Likert scale for medical accuracy and completeness. Statistical analysis involved the Mann-Whitney U test and the Kruskal-Wallis test, followed by pairwise comparison. RESULTS: The combined question-case mean rank for accuracy was 506.2 for the LLM chatbot and 403.4 for glaucoma specialists (n = 831; Mann-Whitney U = 27976.5; P < .001), and the mean rank for completeness was 528.3 and 398.7, respectively (n = 828; Mann-Whitney U = 25218.5; P < .001). The mean rank for accuracy was 235.3 for the LLM chatbot and 216.1 for retina specialists (n = 440; Mann-Whitney U = 15518.0; P = .17), and the mean rank for completeness was 258.3 and 208.7, respectively (n = 439; Mann-Whitney U = 13123.5; P = .005). The Dunn test revealed a significant difference between all pairwise comparisons, except specialist vs trainee in rating chatbot completeness. The overall pairwise comparisons showed that both trainees and specialists rated the chatbot's accuracy and completeness more favorably than those of their specialist counterparts, with specialists noting a significant difference in the chatbot's accuracy (z = 3.23; P = .007) and completeness (z = 5.86; P < .001). CONCLUSIONS AND RELEVANCE: This study accentuates the comparative proficiency of LLM chatbots in diagnostic accuracy and completeness compared with fellowship-trained ophthalmologists in various clinical scenarios. The LLM chatbot outperformed glaucoma specialists and matched retina specialists in diagnostic and treatment accuracy, substantiating its role as a promising diagnostic adjunct in ophthalmology.
, Jhaveri CD, Liu D, Maguire MG, Glassman AR, Grigorian RA, Jampol LM, Kingsley RM, MacCumber MW, Martin DF, Maturi RK, Velez G, Sun JK, Sun JK. Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity. Ophthalmology 2024;Abstract
OBJECTIVE: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network Protocol AC. DESIGN: Post hoc analysis of data from a randomized clinical trial PARTICIPANTS: 270 participants with one or both eyes with CI-DME and visual acuity (VA) letter score of 69 to 24 (Snellen equivalent 20/50-20/320) METHODS: Eligible eyes were assigned to receive intravitreal aflibercept monotherapy (N=158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (N=154). MAIN OUTCOME MEASURES: Meeting switching criteria: 1) at any time, 2) at 12 weeks, and 3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. RESULTS: In the bevacizumab first group, older participants had higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age (95% confidence interval) of 1.32 (1.11 - 1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (HR for male vs. female = 4.84 [1.32 - 17.81]; HR for 5-letter lower baseline VA: 1.30 [1.03 - 1.63]). Worse 12-week CST (HR for 10-μm greater = 1.06 [1.04 - 1.07]) was associated with increased risk for switching after 12 weeks. The mean (SD) improvement after completing the switch to aflibercept was 3.7 (4.9) letters. CONCLUSIONS: The identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At twelve weeks, thicker central subfield thickness was predictive of eyes most likely to be switched in the future.
Wróblewska-Czajka E, Dobrowolski D, Wylęgała A, Jurkunas UV, Wylęgała E. Outcomes of Boston Keratoprosthesis Type I Implantation in Poland: A Retrospective Study on 118 Patients. J Clin Med 2024;13(4)Abstract
Background: Boston Keratoprosthesis Type I (BI-KPro I) is a synthetic cornea that can be used to restore vision in patients with corneal blindness. This retrospective study evaluated the outcomes of BI-KPro implantation in 118 patients. Material: The mean age of the patients was 56.76 ± 14.24 years. Indications for keratoprosthesis implantation were as follows: graft failure, 47 (39.83%); ocular burn, 38 (32.20%); neurotrophic keratopathy, 11 (9.32%), mucous membrane pemphigoid 9 (7.67%); autoimmune, 6 (5.08%); Stevens-Johnson syndrome, 4 (3.39%); and aniridia (2.54%). Methods: The surgeries were performed between March 2019 and June 2022 at a single clinical center in two locations. The postoperative visual acuity, complications, and need for additional surgical procedures were analyzed. Results: The Best Corrected Visual Acuity before surgery was 0.01 ± 0.006. After one year (V1), it was 0.30 ± 0.27; at two years (V2), it was 0.27 ± 0.26; and at three years (V3), it was 0.21 ± 0.23. The percentage of patients with visual acuity better than 0.1 on the Snellen chart was 37.29% after 1 year, 49.35% after 2 years, and 46.81% after 3 years of follow up. The most common complications were glaucoma (78 patients; 66.1%), corneal melting (22 patients; 18.6%), and retroprosthetic membranes (20 patients; 17.0%). Conclusions: The BI-KPro can significantly improve visual acuity. The worst long-term results were obtained in the group of patients with autoimmune diseases; therefore, careful consideration should be given to implanting BI-KPro in this group. The high incidence of de novo glaucoma or the progression of pre-existing glaucoma suggests the need for careful monitoring.
Vujosevic S, Fantaguzzi F, Silva PS, Salongcay R, Brambilla M, Torti E, Nucci P, Peto T. Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion. Eye (Lond) 2024;Abstract
OBJECTIVES: To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. METHODS: In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI's extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10-15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). RESULTS: Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05). CONCLUSIONS: Perfusion macular metrics on OCT-A correlated with UWF-FA's non-perfusion (NP), particularly in the retina's mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.
Syed ZA, Tomaiuolo M, Zhang Q, Prajna V, Hyman L, Rapuano CJ, Rapuano CJ. Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS® Registry Analysis. Ophthalmology 2024;Abstract
PURPOSE: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age between 2015-2020 and evaluate sociodemographic associations with treatment approach. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight). METHODS, INTERVENTION, OR TESTING: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression. MAIN OUTCOME MEASURES: Outcomes included percentages and rates of each treatment (either collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type. RESULTS: 66,199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05% in 2015 to 29.5% in 2020 (P=0.008). The average age (SD) of KCN patients decreased from 44.1 (± 16.9) years in 2015 to 39.2 (± 16.9) years in 2020 (P<0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age; e.g., comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95% CI) decreased from 0.62 (0.57-0.67, P<0.0001) for patients 21-40 years to 0.03 (0.02-0.04, P<0.0001) for patients older than 60. Males were more likely than females to have CXL (OR=1.31, 95% CI 1.23-1.40, P<0.0001) and keratoplasty (OR=1.30, 95% CI 1.19-1.42, P<0.0001). Black patients were less likely than White patients to have CXL (OR=0.70, 95% CI 0.63-0.77, P<0.0001) and more likely to have keratoplasty (OR=2.24, 95% CI 2.01-2.50, P<0.0001). Similarly, Hispanic patients had higher odds of CXL (OR=1.12, 95% CI 1.00-1.24, P<0.05) and keratoplasty (OR=1.29, 95% CI 1.12-1.50, P<0.001) compared to non-Hispanic patients. CXL and keratoplasty also varied by region and insurance status. CONCLUSIONS: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, utilization, or care patterns, and future studies should aim to identify strategies to improve access for all patients.
Lin LY, Azad AD, Chiou CA, Kozanno L, Stemmer-Rachamimov A, Stone J, Lee NG. Antisynthetase Syndrome Causing Necrotizing Myositis Involving Extraocular Muscles. Ophthalmic Plast Reconstr Surg 2024;Abstract
The authors describe the clinical, histologic, and serologic findings of a patient with necrotizing myositis of the extraocular muscles in the setting of antisynthetase syndrome, as well as subsequent management. This is the first case in the literature of a systemic necrotizing myositis to have associated ophthalmic findings.
Hoppe C, Gregory-Ksander M. The Role of Complement Dysregulation in Glaucoma. Int J Mol Sci 2024;25(4)Abstract
Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies.

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